5-61332294-C-A

Variant names:

• chr5-61332294-C-A
• rs1483067522
• NM_020928.2:c.22C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020928.2(ZSWIM6):​c.22C>A​(p.Pro8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000984 in 1,016,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: ZSWIM6 NM_020928.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

ZSWIM6 (HGNC:29316): (zinc finger SWIM-type containing 6) The protein encoded by this gene contains a zinc finger SWI2/SNF2 and MuDR (SWIM) domain. Proteins with SWIM domains have been found in a diverse number of species and are predicted to interact with DNA or proteins. Mutations in this gene result in acromelic frontonasal dysostosis. [provided by RefSeq, Apr 2017]

LOC105378994 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12533784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM6	NM_020928.2	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 14	ENST00000252744.6	NP_065979.1
LOC105378994	XR_007058781.1	n.-78G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM6	ENST00000252744.6	c.22C>A	p.Pro8Thr	missense_variant	Exon 1 of 14	5	NM_020928.2	ENSP00000252744.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.84e-7 AC: 1 AN: 1016434 Hom.: 0 Cov.: 28 AF XY: 0.00000208 AC XY: 1 AN XY: 480472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.00085	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.014
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.25	B
Vest4		0.23
MutPred		0.24		Gain of phosphorylation at P8 (P = 0.0271);
MVP		0.061
MPC		0.55
ClinPred		0.28	T
GERP RS		0.79
Varity_R		0.10
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1483067522; hg19: chr5-60628121;